Gain-of-Function research: Friend or foe?

In late 2019, a distressing crisis was thrust upon the world forever altering our lives. The COVID-19 pandemic rapidly spread across the globe causing fear and sickness, leaving millions mourning the loss of loved ones. As the world grappled with catastrophe, questions arose about what could have been done to prevent such a devastating outcome.

One topic that was brought to the public’s attention, as often happens during times of pathogenic threats, is the controversial topic of Gain of Function research (GoF). GoF research is a type of scientific and medical research that genetically alters a virus, bacteria, or other infectious agent to enhance certain functions of that organism. These modifications can alter the pathogen’s transmissibility (how easily the pathogen can be transmitted between hosts) or pathogenicity (how harmful it is to the host).

GoF research has always been a double-edged sword, with its potential to revolutionize healthcare and the potential risks it poses. As society has explored the pros and cons of GoF research, we have gained insights into its potential benefits and risks.

On one hand, GoF research has proved instrumental in enhancing our understanding of pathogens and infectious diseases. The knowledge gained from such research has led to the development of life-saving vaccines for various viruses, including the SARS-CoV-2 virus responsible for the COVID-19 pandemic. Moderna and Pfizer-BioNTech both utilized GoF research to study and manipulate the SARS-CoV-2 virus to better understand it. They discovered that the virus’s spike protein is crucial for viral entry into human cells. Once the scientists learned the behavior of the virus, they were able to develop a vaccine that prevents its entry into our cells. Similarly, GoF research has also contributed to the development of other vaccines for influenza, Ebola, and Zika viruses.

"As we move forward, the scientific community must strike a delicate balance between progress and responsibility, ensuring that the pursuit of knowledge does not compromise our safety or the well-being of future generations."

--Max Cook

Moreover, GoF research has been crucial in identifying potential pandemic threats in advance, enabling proactive measures to be taken to mitigate the potential devastation of these threats. By using GoF research to analyze the behavior of pathogens, we are equipped to prepare for and respond to future outbreaks and even bioterrorism attacks. For example, in 2012, GoF research was advantageously used to identify the H5N1 strain of avian influenza as potentially becoming more transmissible between humans. Scientists discovered that if specific gene changes occurred in the H5N1 strain, its transmissibility would increase. These findings allowed the government to closely monitor the spread of the virus to track the transmissibility of the H5N1 strain. By identifying pandemic threats before they occur, we can properly prepare for and respond to outbreaks.

GoF research can also play a role in defense plans to counter bioterrorism by studying how pathogens can be manipulated to become more dangerous. For example, anthrax has been used before in bioterrorist attacks. The anthrax used in these attacks is composed of spores from a specific bacterium. These spores are a dormant form of the bacteria which can be activated when inhaled or ingested, leading to severe illness or death. Scientists have used GoF research to create vaccines and antibiotics that are effective in preventing and treating anthrax infections.

In addition to GoF’s contributions to infectious disease research, it has also provided invaluable insights into basic science and molecular interactions. By exploring signaling pathways and host-pathogen interactions, scientists have unlocked therapeutic targets that hold great promise for medical advancements. For instance, understanding the molecular interactions of HIV has paved the way for the development of targeted antiretroviral therapies, significantly improving the lives of those affected by the virus.

However, despite the potential benefits, GoF research is not without its hazards. One of the most concerning aspects is the risk of laboratory accidents. Manipulating pathogens to study their behavior could lead to uncontrolled outbreaks by the potential escape of these augmented pathogens from the lab. 

"Only through vigilant oversight, stringent safety measures and open dialogue can we navigate this precarious territory and harness the full potential of biomedical research without succumbing to its dark side."

--Max Cook

Precautions and safety protocols are in place to limit laboratory accidents, such as using personal protective equipment, training personnel, disregarding waste properly, and performing GoF research in specialized laboratories that prevent the release of pathogens into the environment.  While laboratory accidents are rare, the consequences can be extreme. For example, if scientists increased the transmissibility and pathogenicity of a virus to study it and lab personnel became infected with the modified virus, the virus could spread more quickly and be more fatal than its natural counterpart.

Equally worrisome is the potential misuse of GoF research for bioterrorism, which refers to the use of biological agents such as viruses, bacteria, or other microorganisms, to cause harm.  While existing biological agents already pose a threat, GoF research could be used to engineer even deadlier and more contagious pathogens, making it difficult to use vaccines and antibiotics that have already been developed.

Furthermore, the ethical concerns surrounding GoF research are significant. The power to manipulate pathogens comes with immense responsibility, and the line between advancing science for the greater good and endangering humanity becomes increasingly blurred. The potential for unintended consequences, where a well-intentioned study results in the creation of a more dangerous pathogen, raises moral questions about the true value of such research.

It is crucial for scientists, as well as the public, to have a thorough understanding of the pros and cons of GoF research. This is especially true for GoF research conducted in the US because it is often viewed as a major player in setting standards for ethical research norms. When conducting GoF research, scientists must follow the strict safety protocols stated previously to protect themselves and the public, as well as remain ethical. In conclusion, GoF research should only be done when the potential risks and benefits have been weighed and the benefits are significantly greater to society than the potential harm that could be done.

In conclusion, biomedical research, particularly GoF studies, presents a complex landscape of promise and danger. While it has undeniably contributed to our understanding of pathogens and infectious diseases, the risks associated with GoF research are not to be taken lightly. As we move forward, the scientific community must strike a delicate balance between progress and responsibility, ensuring that the pursuit of knowledge does not compromise our safety or the well-being of future generations. The benefits of GoF are undeniable, but so are the ethical challenges it poses. Only through vigilant oversight, stringent safety measures and open dialogue can we navigate this precarious territory and harness the full potential of biomedical research without succumbing to its dark side.